Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway

Sondermann, Natalie C.; Faßbender, Sonja; Hartung, Frederick; Hätälä, Anna M; Rolfes, Katharina M.; Vogel, Christoph F.A.; Haarmann‐Stemmann, Thomas

doi:10.1016/j.bcp.2022.115371

Cited by 57 publications

(22 citation statements)

References 331 publications

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“…Modulating activity has been considered an essential parameter of verifying the adaptation of transcription factors to exogenous stress, 25 and the signaling is thought to be regulated at three levels as follows: proteasomal degradation of the AhR, AhR-ARNT complex disruption by the AhR repressor (AHRR), and ligand metabolism by CYP enzymes. 26 Agonists and antagonists are commonly used to study the regulatory activity of transcription factors. However, there are few regulators used to investigate the transcription factor AhR, especially in insects.…”

Section: ■ Introductionmentioning

confidence: 99%

Transcription Factor AhR Regulates Glutathione S-Transferases Conferring Resistance to lambda-Cyhalothrin in Cydia pomonella

Liu

Zhang

et al. 2023

J. Agric. Food Chem.

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Aryl hydrocarbon receptor (AhR) enhances insect resistance to insecticides by regulating the detoxification network. Our previous studies have confirmed that overexpressions of cytochrome P450 monooxygenases (P450s) and glutathione S-transferases (GSTs) are involved in lambda-cyhalothrin resistance in Cydia pomonella. Here, we report that CpAhR regulates the expression of GST and P450 genes, thus conferring resistance. Expression patterns indicated that the expression of CpAhR was highly induced by lambda-cyhalothrin exposure and upregulated in a lambda-cyhalothrin-resistant population. RNA interference (RNAi) of CpAhR decreases the expression of key resistance-related genes (CpGSTe3, CpCYP9A121, and CpCYP9A122) and the activity of the GST enzyme, reducing the tolerance to lambda-cyhalothrin. Furthermore, β-naphthoflavone, a novel agonist of AhR, was first proven to be effective in increasing CpAhR expression and larval tolerance to lambda-cyhalothrin. These results demonstrate that CpAhR regulates the expression of key detoxifying genes and GST activity, resulting in the development of resistance to lambda-cyhalothrin in C. pomonella.

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Section: ■ Introductionmentioning

confidence: 99%

Transcription Factor AhR Regulates Glutathione S-Transferases Conferring Resistance to lambda-Cyhalothrin in Cydia pomonella

Liu

Zhang

et al. 2023

J. Agric. Food Chem.

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“…[ 47,48 ] The results demonstrated an elevated expression of CYP2E1 at 0.2 µM, and an ~90% reduction in expression at 2 and 20 µM of pesticide, compared to the control culture. The same pattern of gene expression was observed for the AHR (a gene that produces a protein that regulates xenobiotic‐metabolizing enzymes and works as a transcriptional factor for genes correlated with several metabolic routes even lipid metabolism) [ 49,50 ] and CAR gene (molecule that processes toxic molecules in the organism and also collaborates in glucose and lipid metabolism). [ 49 ] The AHR and CAR genes presented significant increases in their expression at 0.2 μM fipronil concentration and a significative reduction in cells incubated with 2 and 20 μM of the pesticide (~80% reduction to CAR and more than 60% reduction to AHR gene expression levels) when compared to the control.…”

Section: Resultsmentioning

confidence: 68%

Cellular and molecular effects of fipronil in lipid metabolism of HepG2 and its possible connection to non‐alcoholic fatty liver disease

Pansa,

Molica,

de Oliveira Júnior

et al. 2023

J Biochem & Molecular Tox

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Nonalcoholic fatty liver disease (NAFLD) is a global public health problem that affects more than a quarter of the population. The development of this disease is correlated with metabolic dysfunctions that lead to lipid accumulation in the liver. Pesticides are one of etiologies that support NAFLD establishment. Therefore, the effects of the insecticide fipronil on the lipid metabolism of the human hepatic cell line, HepG2, was investigated, considering its widespread use in field crops and even to control domestic pests. To address the goals of the study, biochemical, cellular, and molecular analyses of different concentrations of fipronil in cell cultures were investigated, after 24 h of incubation. Relevant metabolites such as triglycerides, glucose levels, β‐oxidation processes, and gene expression of relevant elements correlated with lipid and metabolism of xenobiotics were investigated. The results suggested that at 20 μM, the pesticide increased the accumulation of triglycerides and neutral lipids by reducing fatty acid oxidation and increasing de novo lipogenesis. In addition, changes were observed in genes that control oxidative stress and the xenobiotic metabolism. Together, the results suggest that the metabolic changes caused by the insecticide fipronil may be deleterious if persistent, favoring the establishment of hepatic steatosis.

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“…The aryl hydrocarbon receptor (AhR) belongs to the basic helixloop-helix (bHLH) family and functions as a transcription factor that is activated through binding with its cognate ligand. This activation is involved in regulating host immune homeostasis and metabolism (1). Since its discovery by Alan Poland in the mid-1970s, the AhR signaling pathway has been extensively studied in various fields, including biology, immunology, and pathophysiology (2).…”

Section: Introductionmentioning

confidence: 99%

Role of aryl hydrocarbon receptors in infection and inflammation

Xu,

Lin,

Xie

et al. 2024

Front. Immunol.

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The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by various ligands, including pollutants, microorganisms, and metabolic substances. It is expressed extensively in pulmonary and intestinal epithelial cells, where it contributes to barrier defense. The expression of AhR is pivotal in regulating the inflammatory response to microorganisms. However, dysregulated AhR expression can result in endocrine disorders, leading to immunotoxicity and potentially promoting the development of carcinoma. This review focuses on the crucial role of the AhR in facilitating and limiting the proliferation of pathogens, specifically in relation to the host cell type and the species of etiological agents involved in microbial pathogen infections. The activation of AhR is enhanced through the IDO1-AhR-IDO1 positive feedback loop, which is manipulated by viruses. AhR primarily promotes the infection of SARS-CoV-2 by inducing the expression of angiotensin-converting enzyme 2 (ACE2) and the secretion of pro-inflammatory cytokines. AhR also plays a significant role in regulating various types of T-cells, including CD4+ T cells and CD8+ T cells, in the context of pulmonary infections. The AhR pathway plays a crucial role in regulating immune responses within the respiratory and intestinal barriers when they are invaded by viruses, bacteria, parasites, and fungi. Additionally, we propose that targeting the agonist and antagonist of AhR signaling pathways could serve as a promising therapeutic approach for combating pathogen infections, especially in light of the growing prevalence of drug resistance to multiple antibiotics.

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Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway

Cited by 57 publications

References 331 publications

Transcription Factor AhR Regulates Glutathione S-Transferases Conferring Resistance to lambda-Cyhalothrin in Cydia pomonella

Transcription Factor AhR Regulates Glutathione S-Transferases Conferring Resistance to lambda-Cyhalothrin in Cydia pomonella

Cellular and molecular effects of fipronil in lipid metabolism of HepG2 and its possible connection to non‐alcoholic fatty liver disease

Role of aryl hydrocarbon receptors in infection and inflammation

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